1. Preclinical Research
An ultra-long-acting oral treatment for opioid use disorder (PIs Comer)
Due to the poor oral bioavailability of buprenorphine, an oral formulation to treat Opioid Use Disorders (OUD) has not been thought possible. An oral dosage form developed by Lyndra Therapeutics’ may provide once weekly oral dosing of buprenorphine. The goal of this project is to evaluate the PK, safety, and preliminary efficacy of this novel dosage formulation in reducing intravenous fentanyl and heroin taking behavior in laboratory animals.
2. Human Behavioral Laboratory
Clinical Trials of Multivalent Opioid Vaccine Components (PI: Comer)
The current study is designed to examine a new approach to treating OUD, namely use of a vaccine targeted against oxycodone [Oxy(Gly)4-sKLH], one of the most commonly abused prescription opioids. The vaccination approach to treating substance use disorders relies on the ability of the vaccine to produce antibodies that bind the target drug in blood and reduce its ability to enter the brain.
Isolation of opioid-specific B cell lymphocytes and development of human opioid-specific monoclonal antibodies (PI: Comer)
The goal of this pilot study is to characterize opioid-specific B cells in opioid users and to demonstrate that opioid-specific B cell frequency is higher in opioid users than opioid-naïve controls. Additionally, opioid-specific B cells will be used to generate monoclonal antibodies against opioids. Generation of opioid-specific monoclonal antibodies will provide proof of concept that B cells bind opioids and can generate functional opioid-specific antibodies.
A Randomized, Double-blind, Placebo- and Active Controlled, Crossover Study to Evaluate the Abuse Potential of Oxymorphone Compared to Other Mu Opioid Agonists in Physically Dependent Opioid Users with Moderate-to-Severe Opioid Use Disorder (PI: Comer)
Significant public health concerns have arisen from the misuse of oxymorphone, a potent mu opioid pain medication approved by the Food and Drug Administration as Opana and Opana ER. However, little is known about its abuse potential relative to other mu opioid analgesics. The present study is designed to examine the abuse liability of intravenous oxymorphone compared to other mu opioid agonists (oxycodone and hydromorphone).
The Ability of Vaped Marijuana to Reduce the Severity of Naloxone-precipitated Withdrawal (PI: Jones).
The study is the first assessment of the ability of the cannabinoid drug to reduce the severity of naloxone-precipitated opioid withdrawal. This proof-of-concept investigation proposes a new pharmacological approach that could greatly improve the tolerability of this opioid overdose treatment by combining it with another medication.
Pilot Study: Developing a Model for Evaluating Overdose Prevention Training Performance (PI: Brandt)
Overdose Education and Naloxone Distribution (OEND) has become a critical approach to address the evolving opioid overdose epidemic. However, it is largely unknown how well laypeople are able to replicate overdose response steps they learn during these brief, didactic trainings in a high-stakes and stressful overdose situation. This project will break new ground by developing and validating a simulation procedure at a state-of-the-art medical simulation center that models a realistic overdose scenario along with a method of rating the overdose response performance of individuals with opioid use disorder after receiving OEND.
A pilot study on the effects of repetitive Transcranial Magnetic Stimulation (rTMS) on Cognitive Impairment in Opioid Use Disorder (PI: Castillo)
This project seeks to evaluate the therapeutic potential of repetitive transcranial magnetic stimulation (rTMS) for improving cognition and helping people with Opioid Use Disorder (OUD) engage in treatment. Other studies have shown that people with a diagnosis of OUD can have thinking impairments, including executive function, memories related to location and seeing, and memory related to keeping an idea in mind or remembering a set of numbers. At the same time, a number of rTMS studies have shown that stimulation of a certain part of the brain, the left dorsolateral prefrontal cortex (the region in charge of these cognitive functions) can improve an individual’s thinking ability. Subjects will be assigned to active vs sham groups and cognitive testing will be performed before and after rTMS. Our hypothesis is that an improvement in cognitive functioning will occur in the active rTMS group compared to the sham group.
Randomized Controlled Trial of Extended-release Buprenorphine vs. Sublingual Buprenorphine for the Treatment of Opioid Use Disorder Patients Using Fentanyl (PI: Levin)
The proposed study is 12-week, randomized, open-label study comparing extended-release buprenorphine (Sublocade) to standard therapy (sublingual buprenorphine), to see if Sublocade will be more helpful in treating opiate use for individuals testing positive for fentanyl and related high potency drugs (HPSO). We plan to enroll 40 participants into the study.
A Randomized, Controlled, Open-Label, Decentralized Study, to Evaluate Patient Engagement with PEAR-008, a Game-Based Digital Therapeutic for the Treatment of Opioid Use Disorder (Site PI: Campbell)
The purpose of this study is to evaluate how individuals use and engage with a game-based mobile application [referred to as PEAR-008] that is designed to treat opioid use disorder. PEAR-008 is a new version of reSET-O, an FDA-authorized mobile application treatment (available by prescription only) for opioid use disorder. Specifically, the study will investigate if changing the application’s delivery format and enhancing content affects how participants use and interact with the intervention. The study population will consist of approximately 130 individuals with opioid use disorder (based on DSM-5 criteria) who have recently started buprenorphine treatment (on their own). Participants will be virtually recruited and randomly assigned to receive either the game-based treatment (PEAR-008) or the original, FDA-authorized treatment (reSET-O). All study visits are virtual, and the duration of the study is 12 weeks.
Efficacy of Buprenorphine and XR-Naltrexone Combination for Relapse Prevention in Opioid Use Disorder (NIH HEAL Initiative) (PIs: Shulman, Bisaga)
This study will evaluate the effectiveness of a new pharmacological approach to increase efficacy of usual treatment with XR-naltrexone for treatment of individuals with opioid use disorder by combining it with buprenorphine. Adding buprenorphine after the patient initiated XR-naltrexone will not produce mu opioid agonist effect but kappa antagonist effects of buprenorphine may provide additional relief of protracted withdrawal, craving, and mood disturbances persisting in patients treated with XR-naltrexone and possibly contributing to premature treatment discontinuation and relapse. This is a parallel arm, double-blind, placebo-controlled study (n=120) to examine whether addition of buprenorphine will improve treatment retention, reduce opioid craving, and improve mood over 24 weeks of treatment with XR-naltrexone administered every four weeks.
A Multi-Center Safety Study examining the use of the O’Neil Long Acting Naltrexone Implant (OLANI) in opioid dependent persons receiving repeat dosing (PIs: Bisaga, Nunes)
This NIDA-funded HEAL UH3 Phase II/III, multi-center, single-arm, open-label study will evaluate the safety and effectiveness profile of the OLANI when used in participants with opioid use disorder (OUD) voluntarily seeking relapse-prevention treatment with the naltrexone implant. All participants will receive two OLANI implants administered via a minor surgical procedure in the lower abdomen area; with one implant inserted subcutaneously on each side from the midline. Approximately 16 weeks after the initial implantation, all participants who tolerated and benefited from the initial treatment will be encouraged to receive a second implantation procedure and continue with research assessments for a total of approximately 48-weeks. At the end of the dosing periods, implants are left in site to gradually dissolve. Participants will be recruited throughout the US, at 4 sites with experience providing naltrexone-based treatment of OUD and OUD treatment research.
Glutamatergic Modulation to Facilitate Naltrexone Initiation: A randomized, controlled trial (PI: Dakwar)
A clinical trial investigating ketamine v. midazolam to improve outcomes in opioid-dependent individuals engaged in a rapid non-opioid-based oral naltrexone titration, followed by extended-release naltrexone (XR-NTX) maintenance. If successful, this trial would represent a major advance in efforts to identify novel pharmacotherapies for opioid use disorder management, and for addressing the critical time and financial hurdles associated with traditional detoxification periods prior to XR-NTX initiation.
Investigating Neurocognitive Impairments after Non-fatal Opioid Overdoses (PI: Castillo)
We would like to better understand if overdoses affect a person's thinking, memory, and ability to understand the world around them. To do this, we want to study how people who have experienced an overdose do on a series of tests that measure different thinking abilities such as memory, planning, and completing tasks. We will compare the results of the group of people who have overdosed before and after completing the Cognitive Bias Modification (CBM), a novel and promising computer-based task designed to directly target implicit cognitive biases to see whether it improves thinking abilities.
Cognitive Functioning in Opioid Use Disorder: Examining the Impacts of Computerized Working Memory Training and Non-Fatal Opioid Overdose (PI: Luba)
This pilot study will examine the utility of a computerized working memory training program on cognitive functioning and impulsive decision making among individuals with OUD with a history of non-fatal opioid overdose. This study will also examine the impacts of non-fatal opioid overdose on cognitive functioning at baseline and explore whether number of prior overdoses and recency of overdose influence response to the training program.
Opioid Response Network (Subaward PI: Levin; Subproject PI: Williams)
Funded by the SAMHSA to AAAP (formerly the STR/SOR) to ensure the provision of evidence-based prevention, treatment and recovery support programs/services across all states and territories, this subaward supports a team of OUD Cascade of Care experts to provide technical assistance to state agencies and large treatment systems to improve data collection and reporting efforts to monitor the opioid crisis.
Improving the treatment cascade of MAT initiation and retention for opioid use disorder (PI: Williams)
This NIDA K23, 5-year study has merged EHR data from a large multi-state, multisite buprenorphine outpatient clinic with Medicaid claims for ~40,000 patients who were treated between 2008-2019 for opioid use disorder in order to investigate care trajectories, clinical characteristics, and the occurrence of adverse events under the OUD Cascade of Care public health framework.
Sexual and Gender Minorities’ Attitudes About, Experiences with, and Access to Opioid Use-Related Services (PI: Paschen-Wolff)
This is a two-part pilot study (Smithers Funding) to involving a review of U.S. opioid use disorder treatment facilities offering LGBTQ (lesbian, gay, bisexual, transgender, and queer)-specific services to characterize the treatment environment, and qualitative interviews with sexual and gender minority (SGM) individuals to understand attitudes about, experiences with, and access to opioid-related services, including treatment and harm reduction.
a. National Institute on Drug Abuse, National Drug Abuse Treatment Clinical Trials Network (CTN), Greater New York Node (PIs: Nunes, Rotrosen)
CTN-0096: Culturally Centering Medications for Opioid Use Disorder with American Indian and Alaska Native Communities (PIs: Campbell, Venner [UNM], Co-I: Paschen-Wolff)
This formative implementation science study uses community based participatory research methods to develop and test a program level intervention at 4 sites to culturally tailor the delivery of MOUD with Tribal communities.
Empirical Identification and Validation of Surrogate Endpoints for Opioid Use Disorder Treatment Outcome (PI: Brandt)
This project seeks to empirically identify and validate surrogate treatment outcomes for OUD using an aggregate dataset (overall N = 2,650 individuals with OUD) of four large, multisite, pragmatic trials completed NIDA’s Clinical Trials Network.
CTN-0094: Individual Level Predictive Modeling of Opioid Use Disorder Treatment Outcome (PIs: Luo, Feaster [UMiami])
The overall objective of this NIH HEAL secondary data analysis study is to develop and disseminate individual level risk prediction models using a harmonized Big Data collection from three multi-site clinical trials from the CTN. Machine learning methods were deployed to predict specific clinical outcomes (drop out; relapse) for patients treated with MOUD, including methadone, buprenorphine, or extended-release depot naltrexone.
CTN-0097: Surmounting Withdrawal to Initiate Fast Treatment with Naltrexone (SWIFT): Improving the Real-World Effectiveness of Injection Naltrexone for Opioid Use Disorder (NIH HEAL Initiative) (PI’s: Bisaga, Nunes; Co-PI: Shulman)
Inpatient programs are important portals for increasing access to treatment. However, most individuals with opioid use disorder are detoxified but not offered medications to prevent relapse. This randomized-controlled trial will examine whether a rapid-transition protocol to inducting extended release naltrexone (XR-NTX) following detoxification yields a higher proportion of patients successfully receiving the first injection of XR-NTX compared to standard detoxification and naltrexone initiation. This study will also assess facilitators and barriers to implementing rapid XR-NTX initiation. The overall goal is to foster widespread adoption of a 5-7-day protocol for initiation of treatment with XR-NTX at Inpatient/Residential programs.
CTN-100: Optimizing Retention, Duration, and Discontinuation Strategies for Opioid Use Disorder Pharmacotherapy (PI: Nunes; Co-PI: Shulman)
Dropout from treatment is a major barrier to the effectiveness of buprenorphine and extended-release naltrexone for treatment of opioid use disorder (OUD). Clinical trials show that 50% or more of participants drop out of treatment by 3 to 6 months after treatment initiation. Patients who do stay in treatment often eventually ask how long they need to continue medication, and whether it would be safe to discontinue; there is little evidence available to guide clinician’s responses to these questions. This NIH HEAL study will 1) test pharmacologic and behavioral strategies to improve OUD pharmacotherapy treatment retention and to improve outcomes among patients who have achieved stable remission on
CTN-0112: Optimizing Policies To Improve Methadone Maintenance Adherence Long-term (PI: Williams)
The OPTIMMAL study evaluates opioid treatment programs (OTPs) across the country and how loosed regulations following COVID impacted retention and drug use outcomes to determine which patients may be more successful with increased take home schedules and fewer visits in person.
CTN-0126: Longitudinal Follow-up of Individuals with Opioid Use Disorder (PI: Shulman)
The primary aim of the Longitudinal Follow-up of Individuals with Opioid Use Disorder (LFU-OUD) study is to establish initial and long-term feasibility of participant registration, retention, engagement, and data collection in a longitudinal study, linked to participating CTN clinical trials, that follows individuals with OUD. Secondary aims will address key scientific questions using core follow-up data and trial-specific longitudinal data elements for participating trials. Scientific inquiries will be geared toward investigating questions such as: characterizing the long-term course of OUD (outcomes of opioid and other substance use, mortality, functional outcomes and engagement in treatment); evaluating treatment participation status at follow-up, treatment retention over time, and effects of each type of opioid replacement treatment on opioid use and other recovery milestones; and identifying predictors of long-term OUD outcomes (treatment-related factors (e.g., type of MOUD), participant sociodemographic characteristics, and participant clinical factors (e.g., co-occurring psychiatric disorders).
b) HEALing Communities Study (PIS: El-Bassel, Nunes, Feaster, Gilbert)
The NIDA/SAMHSA funded HEALing Communities Study is a multi-site implementation research study with the aim of testing the impact of an integrated set of evidence-based practices across health care, behavioral health, justice, and other community-based settings. The goal of the study is to reduce opioid-related overdose deaths by 40 percent over the course of three years in 67 communities (across four states: NY, MA, KY, OH) highly affected by the opioid crisis in four states to measure the impact of these efforts. The study will also look at the effectiveness of coordinated systems of care designed to increase the number of individuals receiving medication to treat OUD, increase the distribution of naloxone, and reduce high-risk opioid prescribing. Findings will establish best practices for integrating prevention and treatment strategies that can be replicated by communities nationwide.
1. Human Behavioral Laboratory
The effect of rTMS in alcohol use disorder (PI: Wai)
This research project studies a form of non-invasive brain stimulation called transcranial magnetic stimulation (rTMS) as a potential intervention to reduce drinking in a laboratory setting. The drinking behavior of participants with alcohol use disorder is studied before and after a 3-week course of rTMS.
The role of brief potent glutamatergic modulation in addressing problem drinking: a randomized, controlled trial (PI: Dakwar)
A 12-week clinical trial investigating ketamine v. midazolam, coupled with either psychotherapy or clinic visits, for the treatment of alcohol use disorder. This study evaluates the impact of behavioral treatment on enhancing and sustaining the effects of ketamine and will deepen our understanding of the clinical role of ketamine in addressing problem drinking.
Stress Reactivity and Early Trauma Exposure in Transmasculine and Transfeminine Alcohol Users (PI: Collins Reed)
This Smithers-funded pilot will allow us to examine the feasibility of detecting a signal of stress reactivity in transfeminine compared to transmasculine individuals and on alcohol-related behaviors compared to a no-stress control condition, as well as explore the role of trauma history, in TGNB moderate/heavy drinkers, that will then inform a larger-scale project which will aim to directly address the theoretical model.
2. Treatment Efficacy
Improving Alcohol Use Disorder Treatment for Gender Minority Populations (PI: Kidd)
This NIAAA K23 study includes mixed-methods formative work to understand the relationship between interpersonal stress and hazardous drinking among transgender and nonbinary (TGNB) individuals. The study culminates in a clinical trial of a culturally adapted psychosocial intervention for TGNB individuals with alcohol use disorder.
A Double-Blind, Placebo Controlled Trial of Pregabalin for the Treatment of Alcohol Use Disorder (PI: Mariani)
The proposed study is a 10-week double-blind, randomized controlled clinical trial comparing the efficacy of pregabalin to placebo in reducing harmful alcohol consumption. Fifty treatment-seeking participants will be actively drinking at study entry and randomized to treatment with pregabalin in dosages up to 600 mg or placebo, with the hypothesis that pregabalin will be tolerable, safe, and effective in reducing harmful drinking in outpatients who present for treatment actively drinking, but do not require an inpatient detoxification.
Neural and Mobile Assessment of Behavior Change Among Problem Drinkers (PIs: Naqvi, Ochsner, Morgenstern)
Although problem drinkers (PD) are a less severe, highly prevalent sub-type of alcohol use disorder (AUD) who are more likely to undergo reductions in alcohol use, compared to more severe AUD, the underlying mechanisms that maintain PD, as well as the mechanisms that underlie both spontaneous and treatment related behavior change in this population, are not well understood. To address these questions, participants will be sent messages on their phone and asked to respond to questions about their alcohol cravings or attempts to resist them. This will be combined with functional MRI to examine neural correlates of craving and of regulation of craving.
Combining Pregabalin (LYRICA®) with Lofexidine (LUCEMYRATM): Can it Increase the Success of Transition to Naltrexone? (Subaward PIs: Mariani, Levin)
This study is a multi-site, phase II, double-blind placebo-controlled, study to examine whether: 1) Pregabalin (PGB) can be combined with lofexidine (LFX) and reduce opioid withdrawal-related subjective effects; and 2) if safe and effective, can the combination increase the proportion of OUD subjects who transition to XR-Naltrexone. To investigate these objectives, preliminary data on the safety and tolerability of PGB/LFX dose sequencing, and the reduction of opioid withdrawal-related subjective effects, will be obtained in the current trial. We will use a two-arm comparison; PGB/LFX versus LFX/PGB-PLA.
1. Preclinical Studies
Antecedents and Consequences of Cocaine Taking: Impact of Oxytocin (PIs: Evans, Foltin)
Manipulating oxytocin may provide a novel avenue for medication development for cocaine use disorders. The goal of this project is to investigate the role of oxytocin in modulating intravenous cocaine taking behavior in laboratory animals.
A mixed-methods approach to investigating new avenues of HIV treatment and prevention among patients with methamphetamine use disorder (PI: Jones)
This study consists of two investigations among patients with active methamphetamine use disorder. Study A is a quantitative investigation to investigate the frequency and severity of co-morbidities related to methamphetamine abuse, which may impact NNRTls-based HIV-1 pharmacotherapy. Study B is designed to explore attitudes (e.g., feasibility and acceptability) concerning HIV prophylaxis prevention among this high-risk population.
Glutamatergic Modulation to Facilitate the behavioral Treatment of Cocaine Use Disorders. (PI: Dakwar)
The primary aim of this 12-week clinical trial is to assess whether giving two sub-anesthetic infusions of ketamine v. midazolam to cocaine users, integrated into a behavioral treatment platform, will promote abstinence. It will also evaluate the correlation between clinical response and brain-derived neurotrophic factor (BDNF), a peripheral biomarker relevant to ketamine antidepressant response.
Tracking ADHD Symptoms Through the Menstrual Cycle in Women Medicated with Amphetamine Salts (PI: Evans)
This online survey will track ADHD symptoms throughout the menstrual cycle in normally cycling women with ADHD who are currently being treated with amphetamine salts, either Adderall® or Mydais®. We hypothesize that symptoms of ADHD will be more severe during the luteal phase of the menstrual cycle and that women may attempt to compensate for these increases in ADHD symptoms by taking higher doses of their ADHD medication.
1. Human Behavioral laboratory
Neurobehavioral Mechanism of Choices to Smoke Cannabis in Cannabis Use Disorder (PIs: Evans, Bedi)
This project focuses on cannabis smokers to investigate the brain (using fMRI) and behavioral mechanisms of choices for cannabis and an alternative reward (a game of chance) in cannabis smokers with and without Cannabis Use Disorder. We hypothesize that recruitment of more habit-oriented strategies will be greater in cannabis smokers with moderate or severe CUD and this will be predictive of greater functional impairment. Results of this research will contribute to understanding about the brain processes underlying addictions, information that may lead to the development of more targeted treatments.
Cannabis Relapse: Influence of Tobacco Cessation (PI: Haney)
Tobacco smoking is a clinical marker for poor treatment outcome for Cannabis Use Disorder (CUD). Our data suggest that quitting tobacco smoking prior to targeting cannabis smoking may be an effective approach to achieving long-term cannabis abstinence. The outcome of this study has the potential to significantly impact CUD treatment and reduce cannabis relapse in the sizable proportion of tobacco-dependent patients seeking treatment for CUD.
Imaging the Effects of Intermittent Thetaburst Stimulation on Cannabis Self-Administration in Heavy Cannabis Users (PI: Kearney-Ramos)
This NIDA K01 5-year randomized, double-blind, sham-controlled study employs cutting-edge MRI-guided personalized transcranial magnetic brain stimulation (TMS), fMRI scanning, and human behavioral pharmacology techniques in order to investigate the effects of TMS as a tool to normalize cognitive control circuitry in heavy cannabis users and reduce cannabis self-administration in the laboratory (AIM 1) and natural ecology (AIM 3). Further, we will demonstrate neural target engagement and validate the purported neurobiological mechanisms underlying clinical response to this novel TMS protocol by determining whether TMS-induced changes in cannabis self-administration are significantly attributable to (i.e., correlated with) changes in neural drug cue reactivity (AIM 2), which if supported, could reflect a clinically relevant biomarker for predicting and monitoring the therapeutic response to TMS for CUD.
The Effect of Food on the Oral Bioavailability of AEF0117, a CBI signaling specific inhibitor in healthy controls (PI: Haney)
This will be a single center Phase 1 food effect and oral bioavailability study in healthy adult male and female subjects, ages 18-45. The study includes 2 inpatient days, and a total of 7 outpatient visits (6 visits + a follow up visit). Participants will stay in the residential laboratory from the afternoon prior to dosing day 1 and until collection of blood sample 24 h after dosing (day 2) and then be discharged. Participants will be asked to come to the laboratory on an outpatient basis thereafter for collection of blood samples each morning at the days specified. After an overnight inpatient stay in the Residential Laboratory, eligible healthy volunteers will be dosed in the morning between 8 and 9 am with a single oral dose of AEF0117 (1 mg). One group of 24 subjects will be dosed after fasting for 10 hours, while the other group of 24 subjects will be dosed 30 min after consumption of a standardized high fat breakfast, in which 50% of the calories are derived from fat (FDA breakfast).
Imaging of the Effect of Deep rTMS on Brain Activity in Chronic Cannabis Use (PI: Kearney-Ramos)
Heavy cannabis users show reduced brain responses to errors in the dorsomedial prefrontal cortex (DMPFC), a region critical to monitoring errors and resolving cognitive and behavioral conflict. Transcranial magnetic stimulation (TMS) is a non-invasive neuromodulation tool that can be used to selectively increase or decrease cortical and subcortical brain activity. In this Smithers-funded pilot study, double-blind, sham-controlled study employing 11 daily sessions of TMS (namely, 10 Hz rTMS), a 22-day inpatient stay, and human behavioral pharmacology techniques, we will determine whether our 3-week therapeutic TMS protocol designed to enhance DMPFC activity is (1) both feasible and tolerable in a group of heavy, near-daily cannabis users, and (2) effective at significantly reducing their cannabis use, as measured via cannabis self-administration in the laboratory.
2. Pharmacology Pain Laboratory
Effects of Cannabis on Low-dose Oxycodone Abuse Liability and Analgesia (PIs: Arout, Cooper [UCLA])
Two major shifts in health policy are occurring in the United States. Physicians are being urged to limit use of prescription opioids for pain to reduce abuse and overdose. At the same time, significant legislative changes in medical use of cannabis have occurred, with chronic pain being the primary indication for which people use medical cannabis, and the one indication for which there is substantial evidence supporting its use. Over half of medical cannabis users report concomitant prescription opioid use with pain patients reporting that cannabis increases the analgesic effects of opioids. These anecdotal patterns of use have significant implications for pain treatment and public health but are occurring in the absence of high-quality data on the impact of the cannabis-opioid combination on abuse liability, safety, and analgesic effectiveness. This study will provide data on the impact of THC:CBD ratios alone, and in combination with low dose oxycodone on measures of abuse liability and analgesia.
Effects of Repeated High-Cannabidiol Cannabis Administration on Experimental Pain and Abuse Liability in Humans. (PI: Arout)
Chronic pain is a significant public health concern in the U.S., for which prescription opioids have historically been the standard treatment. This has resulted in striking rates of opioid use disorders and fatal overdoses. Identifying non-opioid medications for the management of chronic pain with minimal abuse liability is a public health necessity, and cannabinoids are a promising drug class for this purpose. More than 80% of medicinal cannabis users report pain as their primary medical indication. These patients tend to seek products that are low in delta9-tetrahydrocannabinol (THC; the primary psychoactive, and thus intoxicating, component of cannabis), and high in cannabidiol (CBD), a cannabinoid that purportedly has therapeutic benefit for pain but does not produce intoxicating effects. However, there are few well-controlled human laboratory studies assessing the efficacy of high-CBD cannabis for pain in the context of abuse, and even less is known regarding the effects of daily repeated use of cannabis on pain and its relationship to abuse liability. This study will characterize three potential effects of repeated high-CBD cannabis: 1) if tolerance develops to the abuse-related and analgesic effects; 2) if this tolerance is reversible with 7 days of experimentally-induced abstinence (using cannabis that has < 0.01% THC:CBD); 3) if increased pain sensitivity develops with abrupt cessation of active cannabis use.
Effects of Repeatedly-administered Cannabis on Experimental Pain and Abuse-related Outcomes in Humans. (PI: Arout)
This study will address the same questions as described above, but will ask these questions using cannabis that is high in THC and low in CBD.
A Phase 2B, 8-Week, Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study to Evaluate the Efficacy, Safety and Tolerability of the Fatty Acid Amide Hydrolase (FAAH) Inhibitor PF-04457845 in Adults with DSM-5 Current Cannabis Use Disorder (CUD) (PI: Levin)
This is a randomized, double-blind, placebo-controlled, parallel-group study of the efficacy, safety and tolerability of the Fatty Acid Amide Hydrolase (FAAH) Inhibitor PF-04457845 in adults with DSM-5 current Cannabis Use Disorder (CUD). It is a 4-site study with Columbia University, Johns Hopkins, Medical University of South Carolina and Yale University. Approximately 237 total participants (target of approximately 60 participants at each of the four sites) of both genders and all ethnic/racial and socioeconomic backgrounds will be randomized for a total of 178 participants completing the study (approximately 45 subjects per site).
A Randomized Controlled Trial of Guanfacine-ER for Cannabis Use Disorder (PI: Brezing)
The primary purpose of this study is to investigate the effect of guanfacine-ER on reductions in cannabis use and explore its effects on impulsivity and withdrawal through a hybrid in-person and virtual trial of treatment-seeking individuals with CUD and assessing the feasibility of the virtual components of the study. In light of increases in the use of telehealth following COVID-19, we will make use of the technological applications of virtual video visits, remote administration of medication, and ecological momentary assessments (EMA) in conjunction with once monthly visits to the STARS clinic. This will be a 12-week randomized, double-blind, placebo-controlled trial, of guanfacine compared to placebo for CUD.
CBI Signaling Specific Inhibitor for Cannabis Use Disorder (PI: Levin)
[Starting Winter 2022] The objective of the current proposal is to conduct a 12-week Phase IIb randomized, double-blind, placebo-controlled multisite clinical trial to evaluate whether AEF0117 significantly reduces cannabis use and/or facilitates cannabis abstinence relative to placebo. he 12-week multi-site study comprises a 4-week “grace period”, an 8-week “efficacy ascertainment period”, and a 4-week follow-up. Non-responders will not be counted during the grace period, which is aimed to give patients experience with the medication, allowing them time to significantly change their behavior. Four weeks is also the period during which AEF0117 (once/day) reaches steady state. The Primary endpoint will be the proportion of patients functionally abstinent (using cannabis ≤ 1 day/week) for the duration of the 8-week ascertainment period. Secondary outcomes will include: (1) Complete abstinence (0 use days/week) during the 8-week ascertainment period; (2) Modified early remission from CUD at end of treatment; (3) Quality of life; (4) Modest use (≤ 2 use days/week) during the 8-week ascertainment period; (5) Total number of days of cannabis use during ascertainment period. We will also conduct the complementary non-clinical development necessary to show that the compound meets the safety requirements needed to start large scale Phase III trials.
1. Human Behavioral Laboratory
Electroretinogram: a new human biomarker for smoking cessation treatment (PI: Luo)
This K23 project focuses on developing a new human biomarker, electroretinogram, for dopamine release. The hypothesis is that cigarette smokers who do not respond to contingency management will have a deficit in dopamine release detectable using electroretinogram.
SUBSTANCE USE DISORDER RESEARCH (NON-SPECIFIED)
1. Posttraumatic Stress Disorder
Sphenopalatine ganglion (SPG) block for PTSD (PI: Martinez)
The SPG is a collection of nerve cells connected to the autonomic nervous system that is located in the inner nose. This pilot study investigates SPG block as a potential treatment for decreasing PTSD symptoms in participants with or without comorbid substance use disorders.
2. Social Media
Determining Feasibility of Collecting Facebook and Twitter Language from STARS Screening Participants (PI: Brezing)
The primary purpose of this study is to determine the feasibility of collecting retrospective social media data from participants at STARS and characterize participants use of social media at a large clinical trials site. As part of exploratory analyses, we will use differential language analysis (DLA), an open-vocabulary analysis technique to extract a data-driven collection of words, phrases, and topics as functions of known clinical trials outcomes. This will allow us to explore possible characteristics and analyze user-generated interactions on social media by identifying words and phrases in social media communications that correlate with treatment trial-related behaviors and outcomes in order to aid our understanding of 1) participant specific factors from social media communications that might predict screening completion, enrollment, and drop-out, 2) risk factors, attitudes, and behaviors associated with substance use, and collect, 3) initial observations that can guide future research in the development of potential social media monitoring systems that might improve engagement and address attrition in clinical trials, and 4) SUD outcomes in clinical trials.